Project summary

Nowadays, researches focused towards the beneficial health effects that some dietary components may possess, have raised great attention. Among the bioactivities related to the ingestion of healthy dietary compounds, their possible anti-proliferative activity is gaining importance due to the relevance of cancer as one of the most frequent death causes at present. The possibility of preventing processes related to cancer development thanks to particular diet components, such as phenolic compounds, has opened an important research field. However, the particular mechanisms of action through which these components may exert their anti-proliferative activity in-vivo are greatly unknown. This is mainly due to the fact that common in-vitro assays employed nowadays do not take into consideration important parameters related to digestion, absorption, metabolism and modification of those components after their ingestion. Therefore, it is of utmost importance to precisely know the physiological forms derived from the ingested phenolic compounds that can be actually found in the organism as well as their bioactivity, considering that these chemical structures would be those that could in reality exert a beneficial health effect in-vivo. In this regard, the appliation of Foodomics-based approaches may be of great usefulness to unravel the processes taking place in-vivo. The main objective of this project proposal is to study the anti-proliferative activity and molecular mechanisms of action of dietary phenolics from rosemary and different algae species as well as from their corresponding in-vivo metabolic and degradation products against human colon cancer cells. The selection of these two natural matrices is based on the numerous scientific references existing on the anti-proliferative potential of rosemary polyphenols, although, how these components exert their activity in-vivo is still in doubt (e.g., the bioavailability of these compounds as well as if their anti-proliferative activity is actually related to their metabolites/catabolites generated in-vivo is unknown). Moreover, algae are selected due to the huge potential associated to those organisms as an unexplored novel source of anti-proliferative compounds. In this project, a new strategy which application will allow obtaining a deeper knowledge on how dietary components may exert an anti-proliferative activity against human colon cancer cells is proposed, using the ingestion of rosemary and algae polyphenols as model. Particularly, to develop this new strategy, the use of advanced environmentally friendly extraction techniques is combined with the employment of a dynamic gastrointestinal simulation system and with the use of different in-vitro assays using cell cultures, as well as with powerful Foodomics tools (metabolomics and transcriptomics) and a short pilot intervention study in order to confirm the observations previously made at an in-vitro level. The successful application of this new methodology will provide with a deeper understanding on the phenomena taking place during the ingestion of the studied compounds (digestion, metabolism, absorption and interaction with gut microbiota) and how those phenomena influence the anti-proliferative activity of the native dietary components.

Esquema del proyecto
New methodological approach proposed in the present project.





Research papers published within this project


  1. C. Ibáñez, C. Simó, V. García-Cañas, T. Acuhna, A. Cifuentes (2015) The role of direct high-resolution mass spectrometry in foodomics. Analytical and Bioanalytical Chemistry 407: 6275-6287.
  2. A. Sánchez-Camargo, J.A. Mendiola, A. Valdés, M. Castro-Puyana, V. García-Cañas, A. Cifuentes, M. Herrero, E. Ibáñez (2016) Supercritical antisolvent fractionation of Rosemary extracts obtained by pressurized liquid extraction to enhance their antiproliferative activity. Journal of Supercritical Fluids 107: 581-589.
  3. L. Montero, E. Ibañez, M. Russo, R. di Sanzo, L. Rastrelli, A. Piccinelli, R. Celano, A. Cifuentes, M. Herrero (2016) Metabolite profiling of licorice (Glycyrrhiza glabra) from different locations using comprehensive two-dimensional liquid chromatography coupled to diode array and tandem mass spectrometry detection. Analytical Chimica Acta 913: 145-159.
  4. A. Valdés, V. García-Cañas, E. Kocak, C. Simó, A. Cifuentes (2016) Foodomics study on the effects of extracellular production of hydrogen peroxide by Rosemary polyphenols on the anti-proliferative activity of Rosemary polyphenols against HT-29 cells. Electrophoresis, 37: 1795-1804.
  5. A. Valdés, K.A. Artemenko, J. Bergquist, V. García-Cañas, A. Cifuentes (2016) Comprehensive proteomic study on the antiproliferative activity of a polyphenol-enriched Rosemary extract on colon cancer cells using nanoliquid chromatography-orbitrap MS/MS. Journal of Proteome Research, 15: 1971-195.
  6. Fabián A. Reyes, José A. Mendiola, Sonia Suárez-Alvarez, Elena Ibañez, José M. del Valle Adsorbent-assisted supercritical CO2 extraction of carotenoids from Neochloris oleoabundans paste. J Supercrit Fluids 112 (2016) 7-13
  7. M. Castro-Puyana, A. Perez-Sanchez, A. Valdés, O.H.M. Ibrahim, S. Suarez-Alvarez, J.A. Ferragut, V. Micol, A. Cifuentes, E. Ibáñez, V. García-Cañas (2016) Pressurized liquid extraction of Neochloris oleoabundans for the recovery of bioactive carotenoids with anti-proliferative activity against human colon cancer cells. Food Research International DOI: 10.1016/j.foodres.2016.05.021
  8. T. Acunha, C. Ibañez, V. García-Cañas, C. Simó, A. Cifuentes (2016) Recent advances in the application of capillary electromigration methods for food analysis and Foodomics. Electrophoresis, 37: 111-141.
  9. G.L. Erny, T. Acunha, C. Simó, A. Cifuentes, A. Alves (2016). Finee- A Matlab toolbox for separation techniques hyphenated high resolution mass spectrometry dataset. Chemometrics and Intelligent Laboratory Systems, 155: 138-144.
  10. S. Mazzutti, S.R. Salvador Ferreira, M. Herrero, E. Ibañez (2016) Aqueous based extraction of two plantain species: Plantago major and Plantago laceolata. Journal of Supercritical Fluids. En prensa. DOI: 10.1016/j.supflu.2016.09.008
  11. T. Brazdauskas, L. Montero, P.R. Venskutonis, E. Ibañez, M. Herrero (2016) Downstream valorization and comprehensive two-dimensional liquid chromatography-based chemical characterization of bioactives from black chokeberries (Aronia melanocarpa) pomace. Journal of Chromatography A. En prensa. DOI: 10.1016/j.chroma.2016.09.033
  12. J. Fabrowska, E. Ibáñez, B. Leska, M. Herrero (2016) Supercritical fluid extraction as a tool to valorize underexploited freshwater green algae from Poland. Algal Research. En prensa. DOI: 10.1016/j.algal.2016.09.008
  13. A. Di Loreto, L. Montero, R. Di Silvestro, V. Bregola, I. Marotti, R.E. Sferazza, V. Stenico, G. Dinelli, M. Herrero, S. Bosi, A. Cifuentes. Quantification of free and bound phenolic compounds in old and modern durum wheat varieties using ultra high performance liquid chromatography coupled to tandem mass spectrometry. Journal of Chromatography A.
  14. T. Acuhna, C. Simó, C. Ibáñez, A. Gallardo, A. Cifuentes (2016) Anionic metabolite profiling by capillary electrophoresis-mass spectrometry using a noncovalent polymeric coating. Orange juice and wine as a case of study. Journal of Chromatography A 1428: 326-335.
  15. G.L. Erny, T. Acunha, C. Simó, A. Cifuentes, A. Alves (2016) Algorithm for comprehensive analysis of datasets from hyphenated high resolution mass spectrometric techniques using single ion profiles and cluster analysis. Journal of Chromatography A 1429: 134-141.
  16. A. Valdés, V. García-Cañas, K.A. Artemenko, J. Bergquist, A. Cifuentes (2016) Nano-Liquid Chromatography-Orbitrap MS -Based Quantitative Proteomics Reveals Differences Between the Mechanisms of Action of Carnosic Acid and Carnosol in Colon Cancer Cells. Molecular and Cellular Proteomics (enviado)